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Adenovirus siMDM2 and NDRG2 Gene Therapy Inhibits Cell Proliferation and Induces Apoptosis of Squamous Cell Carcinoma

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Abstract

Squamous cell carcinoma (SCC) is one of the most common skin cancers. In the present study, we explored the effects of depletion of murine double minute gene 2 (MDM2) together with overexpression of N-myc downstream-regulated gene 2 (NDRG2) on cutaneous SCC. In order to achieve high efficiency of gene knockdown and overexpression in SCC-13 cells, recombinant adenovirus carrying siMDM2 and NDRG2 expression construct was produced. We found Ad-siMDM2, Ad-NDRG2, and Ad-siMDM2-NDRG2 infections inhibit the growth of SCC-13 cells in vitro, and Ad-siMDM2-NDRG2 infection has the highest inhibitory effect. Subcutaneous injections of Ad-siMDM2, Ad-NDRG2, and Ad-siMDM2-NDRG2 into SCC-13 xenograft nude mice resulted in the reduction of tumor volume. Moreover, we found that apoptosis protein caspase 3 was up-regulated in the Ad-siMDM2-, Ad-NDRG2-, and Ad-siMDM2-NDRG2-treated groups. Our data indicate that the adenovirus-mediated MDM2 silencing and NDRG2 overexpression can synergistically inhibit local cancer cell proliferation, induce apoptosis, and further prevent metastases of SCC. Our study provides a promising method that can be further developed as a new therapeutic approach against SCC.

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Acknowledgement

This paper has been supported by the NSFC Grant No. 81171492.

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Correspondence to Li Zhang.

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Wang, S., Chen, N., Dong, N. et al. Adenovirus siMDM2 and NDRG2 Gene Therapy Inhibits Cell Proliferation and Induces Apoptosis of Squamous Cell Carcinoma. Cell Biochem Biophys 73, 513–518 (2015). https://doi.org/10.1007/s12013-015-0691-8

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